title: Identification of BACE1 inhibitors from Panax ginseng saponins-An Insilco approach.
abstract: BACE1, a β secretase candidate enzyme, initiates the Alzheimer's disease (AD) pathogenesis via amyloid β (Aβ) peptide production serving as a potential therapeutic target. Previous experimental evidence suggested that ginsenosides, a key component of Panax ginseng, are effective against AD. In this study, we implemented a molecular modeling method to reveal the inhibitory action of ginsenosides on BACE1 activity. We selected 12 ginsenosides and performed molecular docking studies to evaluate its interaction with the BACE1 active site, which is essential for inhibition. Further ADMET filtration was applied to find drug-like molecules with a specific ability to cross blood brain barrier (BBB), and to determine toxicity. The BACE1-ginsenosides complex was further subjected to a molecular dynamics simulation to study the stability of the complex and its hydrogen bond interactions. In summary, our findings show ginsenosides CK, F1, Rh1 and Rh2 are potential BACE1 inhibitors from Panax ginseng.
authors.affiliation: Department of Biochemistry, VRR Institute of Biomedical Science, Chennai-600056, Tamilnadu, India. karpagambio@gmail.com
authors.forename: Veerappan
authors.initials: V
authors.lastname: Karpagam
authors.forename: Natarajan
authors.initials: N
authors.lastname: Sathishkumar
authors.forename: Subramaniyam
authors.initials: S
authors.lastname: Sathiyamoorthy
authors.forename: Periannan
authors.initials: P
authors.lastname: Rasappan
authors.forename: Samuel
authors.initials: S
authors.lastname: Shila
authors.forename: Yeon-Ju
authors.initials: YJ
authors.lastname: Kim
authors.forename: Deok-Chun
authors.initials: DC
authors.lastname: Yang
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D020134:Catalytic Domain; D004355:Drug Stability; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D036145:Ginsenosides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D006860:Hydrogen Bonding; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D005894:Panax / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D004791:Enzyme Inhibitors; D036145:Ginsenosides; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human